Laparoscopic Adrenalectomy for Adrenal Malignancy: A Preliminary Report Comparing the Short-Term Outcomes with Open Adrenalectomy
BORIS KIRSHTEIN, MD,1 JEAN D. YELLE, MD, FRCSC,2 HUSEIN MOLOO, MD, FRCSC,2 and ERIC POULIN, MD, MSc, FRCSC2
ABSTRACT
Background: The laparoscopic approach to adrenal malignancy remains a topic of debate.
Methods: A retrospective analysis of patients who had an open or laparoscopic adrenalectomy for malignancy at a tertiary care center from 1995 to 2005 were included in this study.
Results: Twenty-six cases were identified: 19 women and 7 men with a median age of 48 years (range, 20-81) underwent 12 open (8 adrenocortical carcinoma [ACC] and 4 metastases) and 14 lap- aroscopic adrenalectomies (5 ACC, 8 metastases, and 1 lymphoma). Conversion to open surgery was required in 1 laparoscopic case (7%). Cases with obvious invasion to adjacent organs were not ap- proached laparoscopically. There was no difference in age, sex, American Society of Anesthesiolo- gists status or diagnosis between the two groups, but patients in the laparoscopic group had a higher body mass index. Two patients required splenectomies for splenic tears in the open group. There was no difference in operative time between the two groups, but estimated blood loss (200 vs. 550 mL; P = 0.01) and hospital stay (2 vs. 7 days; P = 0.005) were less in the laparoscopic group. The size of tumors removed by open surgery was larger than by laparoscopy (8 vs. 4 cm; P = 0.003). No locoregional recurrences are reported so far in the laparoscopic group.
Conclusions: Laparoscopic adrenalectomy is both feasible and safe for some malignant tumors of the adrenal gland in experienced hands. However, it cannot be applied to all cases. Careful selec- tion, preoperative staging, and respect for oncologic principles are important considerations in choos- ing laparoscopic surgery for primary and secondary adrenal malignancy. Short-term outcomes are better when the laparoscopic approach is possible. Confirmation and long-term results with further studies are required.
INTRODUCTION
P RIMARY ADRENOCORTICAL CARCINOMA (ACC) is a rare tumor with a poor prognosis. Surgical resection re- mains a potentially curative treatment for localized (stages I and II) disease (Table 1).1,2 When surgical ex- cision is deemed complete, the 5-year survival is reported
to be 32-58%, but when incomplete, the median survival is less than 1 year (range, 2-16 months). Even after an apparent complete resection, local or distant relapse oc- curs in nearly 80% of patients.3,4
The adrenal glands are also common sites of the metastatic spread of different malignancies, and there is the suggestion that resection of single metastases from
1Department of Surgery “A,” Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
2Department of Surgery, The Ottawa Hospital, University of Ottawa, Ontario, Canada.
| Tumor | Nodes | Metastasis |
|---|---|---|
| Type | N0, no lymph nodes involved N1, regional nodes involved | M0, no distant metastasis M1, distant metastasis |
| T1, tumor <5 cm, no invasion of surrounding tissue T2, tumor >5 cm, no invasion T3, local tumor growth without infiltration of adjacent organs | ||
| T4, infiltration of surrounding organs | ||
| Stages | ||
| I, T1 NO MO | ||
| II, T2 N0 M0 | ||
| III, regional extension and or N1 | ||
| IV, distant metastasis |
Adapted from Sullivan M et al.1 and MacFarlane.2
lung, colon, breast cancer, renal cell carcinoma, melanoma, and adrenal glands may improve long-term survival.5-7
Though the laparoscopic adrenalectomy (LA) is con- sidered the gold standard for the surgical treatment of be- nign adrenal pathology, its role in the treatment of can- cer is still debated. Even if lesion size is no longer considered an absolute contraindication for LA, for the laparoscopic approach to be acceptable in the treatment of malignancy, the oncologic principles established with open surgery must be adhered to. In addition, safe spec- imen extraction in a retrieval bag is essential to ensure no peritoneal or wound seeding.8-10 Nevertheless, con- troversy remains with the appropriateness of laparoscopic surgery in patients with primary and secondary adrenal malignancies.
This study compares the short-term clinical outcomes of open and laparoscopic adrenalectomy in order to as- sess its safety and effectiveness in patients with primary and secondary adrenal malignancy treated over the last decade at our center.
PATIENTS AND METHODS
A retrospective chart review of 126 patients who un- derwent an adrenalectomy between January 1995 and November 2005 at our center was performed. Twenty- six (21%) adrenalectomies were performed for malignant lesions: 12 for primary ACC, 13 for metachronous adrenal metastases, and 1 for a retroperitoneal lymphoma closely adherent to the adrenal gland. Patients undergo- ing surgery for synchronous primary tumor and adrenal metastases were excluded from this analysis. Laparo- scopic adrenalectomy was attempted in 14 patients be- tween 1997 and 2005, and open surgery was performed in 12. Adrenal metastases were diagnosed between 1 and 11 years after the resection of the primary tumor or pre- vious metastases, and were discovered during a routine oncologic follow-up. All patients with adrenal metastases had controlled primary disease.
The laparoscopic and open cohorts were compared for tumor type and size, duration of surgery, estimated blood loss, morbidity, hospital stay, and body mass index (BMI). All values are expressed as the median unless oth- erwise stated. The Wilcoxon rank sum test was used to compare the two groups.
RESULTS
Twenty-six patients (19 female, 7 male) with a median age of 48 years (range, 20-81) underwent an adrenalec- tomy for adrenal malignancy. The primary diagnostic imaging modality leading to the diagnosis was ultra- sonography (US) in 12 patients and computed tomogra- phy (CT) in 14. An abdominal CT scan was done in all patients. Magnetic resonance imaging (MRI) was used for additional information in 6 and metaiodobenzyl- guanidine in 1 patient. In 7 of the 12 (58%) patients with ACC, the tumor was found incidentally during the in- vestigation of different unrelated conditions. Only 3 pa- tients with ACC (25%) presented with functioning tu- mors (Table 2).
Tumors were localized in the left adrenal in 16 patients and in the right in 10. ACC was confirmed on histopatho-
| n | |
|---|---|
| Incidentaloma | 7 |
| Unspecific abdominal pain | 2 |
| Pregnancy investigation | 1 |
| Routine investigation | 1 |
| Renal colic | 1 |
| Anemia | 1 |
| Flank pain | 1 |
| Cushing's syndrome | 2 |
| Virilism | 1 |
| Hypertension | 2 |
| Total | 12 |
| Laparoscopic adrenalectomy | Open adrenalectomy | P value | |
|---|---|---|---|
| Male:female | 3:11 | 4:8 | NS |
| Median age (years) | 56 | 40 | 0.2 |
| BMI | 29 | 25 | 0.04 |
| ASA score | 2 | 2 | NS |
| Primary ACC | 5 | 7 | NS |
| Metastases | 8 | 5 | NS |
| Retroperitoneal tumor | 1 | 0 | NS |
| Tumor side (Rt:Lt) | 4:10 | 6:6 | NS |
| Surgery time (minute) | 153 | 170 | NS |
| Estimated blood loss (mL) | 200 | 550 | 0.01 |
| Tumor size (cm) | 4 | 8 | 0.009 |
| Intraoperative complications | 0 | 2 (15%) | NS |
| Hospital stay (days) | 2 | 7 | 0.005 |
BMI, body mass index; ASA, American Association of Anesthesiologists; ACC, adrenal cortical carcinoma; NS, not significant.
logic examination in 13 patients, metastatic tumor in 12, and retroperitoneal tumor closely adherent to the adrenal gland in 1. There was no significant difference between the groups for age, sex, American Society of Anesthesi- ologists (ASA) status, and type of tumor. BMI was higher in the laparoscopic group (29 vs. 25; P = 0.04) (Table 3). There were more ACCs in the open group than in the laparoscopic group (7 vs. 5) and fewer metastases (5 vs. 8) (Table 4).
Laparoscopic transperitoneal adrenalectomy was at- tempted in 14 patients. Conversion to open surgery was necessary in 1 case (7%) due to difficulties in tumor iden- tification and dissection. Twelve patients underwent an open adrenalectomy for the following reasons: 3 had tu- mor invasion into the kidney, 1 required small bowel
| Diagnosis | Number of patients | ||
|---|---|---|---|
| ACC | |||
| Open | 7 | ||
| Laparoscopic | 5 | ||
| Metastasis | |||
| Open | 5 | ||
| Lung | 3 | ||
| Renal cell | 2 | ||
| Melanoma | 1 | ||
| Esophageal | 1 | ||
| Laparoscopic | 8 | ||
| Lung | 3 | ||
| Renal cell | 3 | ||
| Osteosarcoma | 1 | ||
| Leiomyosarcoma uterus | 1 | ||
| Lymphoma | 1 | ||
ACC, adrenal cortical carcinoma.
biopsy, and 1 was the patient’s choice. The remaining 7 cases were done before the laparoscopic approach was used for malignancies.
There was no difference in operating time when com- paring the two groups: 153 minutes (range, 116-280) in the laparoscopic group versus 170 minutes (range, 70-555) in the open group. The estimated blood loss was signifi- cantly lower during the laparoscopic procedure; 200 mL (range, 150-300), versus 550 mL (range, 250-1500) dur- ing open surgery (P = 0.01). Of note is the fact that 2 pa- tients required a splenectomy due to splenic tears during the open adrenalectomy (15%), although there was no sig- nificant difference in intraoperative complication rates be- tween the two groups (Table 3).
Tumors removed by open surgery were larger than in the laparoscopic cases; 8 cm (range, 2.3-15) versus 4 cm (range, 1.7-11.5), respectively (P = 0.009). The hospital stay was significantly lower after laparoscopic surgery: 2 days (range, 1-10) versus 7 days (range, 4-19) (P = 0.005). One patient suffered a myocardial infarction and 1 had atelectasis following the open adrenalectomy.
Only 1 patient with ACC had stage I disease (tumor < 5 cm, no nodes), 8 had stage II (tumor > 5 cm, no nodes) disease, and three stage IV (invasion of kidney). All stage IV patients had an open operation and en bloc nephrec- tomy. No locoregional recurrences have been reported so far in the patients who were selected for the laparoscopic approach.
DISCUSSION
Laparoscopic adrenalectomy is recommended for be- nign tumors and affords a significantly decreased mor- bidity, shortened length of hospital stay, more rapid con- valescence, and improved cosmesis. However, whether
the same laparoscopic approach is appropriate for ma- lignant lesions is a different issue. When laparoscopic adrenalectomy was first introduced, it was considered contraindicated in malignancy.
One of the problems in choosing the surgical approach is the correct preoperative identification and staging of malignant neoplasms of the adrenals. The primary method of radiologic examination in patients with the suspicion of a malignant adrenal lesion is US, where most ACCs can be detected because of the large size of the le- sions. For further preoperative staging, a CT is most of- ten used. For a further differentiation of tissue density and for visualizing the tumor in different planes, an MRI can be useful. MRI can distinguish between ACC and be- nign adrenal adenoma on the basis of signal intensity on T1- and T2-weighted images. Local invasion and infil- tration or a tumor thrombus in the renal vein or the in- ferior vena cava can be revealed or excluded preopera- tively with the use of MRI.11 In 3 patients in this report, tumor invasion of the kidney was strongly suspected and they were all treated by open surgery. Sound judgment needs to be exercized as to the limits of the laparoscopic approach with large invasive tumors, generally ACC. Some large, invasive tumors should not be approached laparoscopically at this point.
Surgical removal has been widely reported as the only effective treatment for ACC, particularly if the diagnosis is made at stages I (tumors <5 cm, no nodes) or II (tu- mors >5 cm, no nodes).12 This is tempered by the fact that the overall median survival for ACC is 25 months and the 5-year actuarial survival is 25%.13 Of note is the fact that the spillage of tumor cells during surgery has been shown to be a cause of recurrence, while breakage of the tumor capsule does not appear to shorten an al- ready limited survival.14,15 Although ACC recurrences occur most frequently at the locoregional level, pul- monary, liver, and bone metastases are also seen. Resec- tion of recurrent tumor or isolated metastases has been documented to prolong survival by some, but not all, studies.16 Accordingly, tumor resectability at the initial surgery is associated with a better overall survival.15
Laparoscopic resection has recently been performed for primary adrenal cancer.10,17-21 However, treatment of adrenal malignancy with laparoscopy is still controver- sial. The average length of disease-free survival after lap- aroscopic adrenalectomy is 34.1 months. Involvement of surrounding tissue or adrenal and caval veins, and a tu- mor size of more than 6 cm, are still viewed, by some, as a contraindication for laparoscopic adrenalectomy. However, others claim that tumor size is only a relative contraindication to the laparoscopic approach.8-10 In our series, the median size of laparoscopically resected ma- lignant lesions was 4 cm, half the median size of tumors removed with open surgery. This reflects the concern by surgeons to strictly follow the principles of oncologic
surgery, including free tumor margins, using retrieval bags for specimen extraction, and wound protection, which are essential steps to lower local recurrence. While local recurrence or intraperitoneal dissemination has been reported in up to 40% of patients having laparoscopic adrenalectomy for malignancy, it has not been seen in this cohort.17 Rapid tumor growth in the adrenal bed was reported in patients with histologic positive margins.22,23 It is still not known whether the frequency of such com- plications differs between conventional and laparoscopic surgical procedures. Popriglia et al.22 and Suzuki et al.23 consider that a low threshold to conversion to open surgery was needed to prevent tumor-cell dissemination in cases of dense adhesions and/or local fixation of the adrenal masses. Cobb et al.17 suggests that locally inva- sive disease is a possible contraindication for the laparo- scopic approach. It also depends on the complexity of the operation and surgeon experience.
The experience of the last decade in this institution seems to indicate that with proper selection, the laparo- scopic approach has short-term advantages with shorter operative time, fewer complications (no iatrogenic spleen injury), less blood loss, and shorter hospital stay. Further, there does not seem to have adverse effects on survival. However, the small number of cases, the obvious selec- tion bias, and the absence of randomization limit the va- lidity of our conclusions.
With the experience to date, it is evident that the lap- aroscopic approach is not desirable or even possible in all cases. Tumor size, local invasion, and side of the tu- mor are some of the factors that need to be considered before a surgical approach is considered in malignant dis- ease. It also seems that because of smaller tumor size and less invasion of the adjacent organs, laparoscopic surgery would be more appropriate for a solitary metastasis than ACC. An early conversion to open surgery also needs to occur if all principles of appropriate oncologic resection cannot be followed laparoscopically. With this in mind, many patients can be treated laparoscopically with the short-term advantages traditionally associated with min- imally invasive surgery and no obvious adverse effects to survival. Further confirmation is required.
CONCLUSIONS
Laparoscopic adrenalectomy is a feasible, safe, mini- mally invasive procedure for some malignant tumors of the adrenal gland in experienced hands. Careful selec- tion, preoperative staging, and adherence to the princi- ples of oncologic surgery are key success factors for lap- aroscopic surgery in primary and secondary adrenal malignancy. Very large tumors or tumors with regional invasion should probably not be approached laparoscop- ically. Smaller ACCs and solitary metastatic lesions lend
themselves to a laparoscopic approach. Short-term out- comes are better in cases selected for the laparoscopic approach. So far, the laparoscopic approach does not have an adverse effect on survival in properly selected patients.
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Address reprint requests to: Boris Kirshtein, MD Department of Surgery “A” Soroka University Medical Center Faculty of Health Sciences Ben-Gurion University of the Negev P.O. Box 151 Beer Sheva, 84101 Israel
E-mail: borkirsh@bgu.ac.il